Dexamethasone for prophylaxis of postoperative nausea and vomiting. A meta-analysis of randomized controlled studies

OBJECTIVE: Randomised controlled trials investigating the efficacy of dexamethasone alone or in combination with other antiemetics to prevent postoperative nausea and vomiting (PONV) were included in a meta-analysis to estimate the relative efficacy of these treatments. METHODS: Studies were systematically searched using Medline, EMBASE, the Cochrane-Library, and by manual screening the reference lists and current issues of locally available anaesthesia journals. Studies identified were divided into four different groups. For each subgroup an independent analysis was performed: 1. Dexamethasone vs. placebo, 2. Dexamethasone + other antiemetic vs. other antiemetic alone, 3. Dexamethasone + other antiemetic vs. dexamethasone alone, 4. Dexamethasone vs. other antiemetics. The main end point in each study was defined as complete absence of nausea, retching, and vomiting after prophylactic antiemetic treatment. The pooled odds-ratios, the relative risk (RR) and the numbers-needed-to-treat (NNT) with their corresponding 95%-confidence intervals (given in parentheses) were calculated using a random effects model. RESULTS: A total of 26 studies with 2561 patients were analysed. 1. As a sole antiemetic agent dexamethasone is superior to placebo to prevent PONV (RR: 0.49 (0.15-0.42); NNT: 3.4 (2.5-5.3)). 2. When dexamethasone and an other antiemetic (e.g. a 5-HT3-antagonist) are combined this drug combination is significantly more effective than the single antiemetic without dexamethasone (RR: 0.60 (0.46-0.78); NNT: 7.3 (5.7-10.2)). 3. A similar result was obtained when the dexamethasone combination was compared with dexamethasone alone. The combination is statistically superior (RR: 0.16 (0.08-0.32); NNT: 3.2 (2.2-6.3)). 4. Dexamethasone was usually compared with 5-HT3-antagonist and to a less extends also with dopamine antagonists. Summarising these studies, there was no significant difference concerning effectiveness (RR: 1.35 (0.99-1.85); NNT: 10.6 (5.6-92.6)). CONCLUSION: Dexamethasone has antiemetics effects that are superior to placebo treatment and are comparable with conventional antiemetic agents (e.g. 5-HT3-antagonist, dopamine antagonists). The drug is especially useful in combination with other antiemetics and increases the efficacy of the antiemetic partner drug.     

Antiemesis After Total Joint Arthroplasty: Does a Single Preoperative Dose of Aprepitant Reduce Nausea and Vomiting?

Background  

Postoperative nausea and vomiting (PONV) is frequent after joint arthroplasty; in addition to causing patient distress, it interferes with early mobilization and hospital discharge. Various antiemetic agents reduce PONV, but their action is limited by a short half-life. Aprepitant, an antiemetic developed for patients receiving chemotherapy, has a duration of action much longer than other antiemetics.     

Physiology and pharmacology of nausea and vomiting

The physiology of nausea and vomiting is poorly understood. The initiation of vomiting varies and may be due to motion, pregnancy, chemotherapy, gastric irritation or postoperative causes. Once initiated, vomiting occurs in two stages, retching and expulsion. The muscles responsible for this sequence of events are controlled by either a vomiting centre or a central pattern generator, probably in the area postrema and the nearby nucleus tractus solitarius. Drugs which induce vomiting include ipecacuanha, a gastric irritant, and apomorphine, a dopamine-receptor agonist. Opioid drugs also induce vomiting, but opioid antagonists are not useful to treat nausea and vomiting. Anti-emetic drugs consist of a variety of neurotransmitter antagonists and may act in the periphery, the central nervous system or both sites. The most important drugs are antagonists at muscarinic, dopamine D₂, 5-HT₃, histamine H₁ and neurokinin NK₁ receptors. These drugs are discussed with particular attention to post-operative nausea and vomiting (PONV).     

Physiology and pharmacology of nausea and vomiting

The physiology of nausea and vomiting is poorly understood. The initiation of vomiting varies and may be due to motion, pregnancy, chemotherapy, gastric irritation or post-operative causes. Once initiated, vomiting occurs in two stages, retching and expulsion. The muscles responsible for this sequence of events are controlled by either a vomiting centre or a central pattern generator, probably in the area postrema and the nearby nucleus tractus solitarius. Drugs which induce vomiting include ipecacuanha, a gastric irritant, and apomorphine, a dopamine-receptor agonist. Opioid drugs also induce vomiting, but opioid antagonists are not useful to treat nausea and vomiting. Anti-emetic drugs consist of a variety of neurotransmitter antagonists and may act in the periphery, the CNS or both sites. The most important drugs are antagonists at muscarinic, dopamine D₂, 5-HT₃, histamine H₁ and neurokinin NK₁ receptors. These drugs are discussed with particular attention to post-operative nausea and vomiting (PONV).     

Effects of different serotonin receptor subtype antagonists on the development of cardiac allograft vasculopathy in murine aortic allografts

BackgroundCardiac allograft vasculopathy (CAV) is the main obstacle for long-term survival after heart transplantation. Alloimmune mediated chronic vascular rejection results in several mechanisms like platelet activation, immigration of inflammatory cells through the endothelial layer and proliferation and migration of smooth muscle cells (SMCs). Serotonin (5-HT) promotes these processes via activation of 5-HT₂ receptors. We hypothesized that inhibiting 5-HT₂ receptors ameliorates the development of CAV.MethodsCBA/JRj mice recieved aortic grafts from C57BL/6 mice. After transplantation until recovery of organs, recipients were treated with serotonin receptor antagonists: sarpogrelate (5-HT_2A), SB 204741 (5-HT_2B) or terguride (5-HT_2A+B). Mice were sacrificed after 14 days for qRT-PCR analysis or after 30 days for histological evaluation. Serum serotonin ELISA was done at both time points.ResultsElevated serum serotonin levels were significantly reduced after 5-HT_2A antagonist treatment as was 5-HT_2A receptor expression. This went along with reduced inflammation characterized by significantly fewer infiltrating macrophages and pro-inflammatory intragraft cytokines and with reduced tissue remodeling evident as significantly less neointima formation.ConclusionInhibition of the 5HT/5-HT_2A receptor axis leads to significantly reduced neointima proliferation after aortic transplantation associated with reduced transendothelial migration of macrophages and decreased expression of inflammatory cytokines. These findings have translational implications as inhibitors of 5HT_2A like sarpogrelate are already approved for clinical use.     

Management of postoperative nausea and vomiting in women scheduled for breast cancer surgery

Breast cancer surgery performed under general anesthesia is associated with a high incidence of postoperative nausea and vomiting (PONV). A number of approaches are available for the management of PONV after breast cancer surgery. First, the risk factors related to patient characteristics, surgical procedure, anesthetic technique, and postoperative care can be reduced. More specifically, the use of propofol-based anesthesia can reduce the incidence of PONV. Secondly, a wide range of prophylactic antiemetics, including butyrophenones (droperidol), benzamides (metoclopramide), glucocorticoids (dexamethasone), clonidine, a small dose of propofol, and serotonin receptor (SR) antagonists (ondansetron, granisetron, tropisetron, dolasetron, ramosetron, and palonosetron), are available for preventing PONV. Thirdly, antiemetic therapy combined with granisetron and droperidol or dexamethasone, and a multimodal management strategy which includes a package consisting of dexamethasone, total intravenous anesthesia with propofol, and ondansetron are highly effective in preventing PONV. Unfortunately, the use of glucocorticoids and SR antagonists for preventing PONV is not permitted in Japan according to national health insurance guidelines. Fourth, electro-acupoint stimulation at the P6 point (Nei-Guwan) as a non-pharmacologic therapy is as effective as ondansetron for preventing PONV. Knowledge of the risk factors for PONV, antiemetics, and a non-pharmacologic approach are needed for the management of PONV in women undergoing breast cancer surgery.     

Klinische Pharmakologie

The rule of three describes three steps which are needed for an optimal control of postoperative nausea and vomiting (PONV). Firstly, patients at high risk of PONV need to be identified. Knowledge about predictive factors may help to identify patients who may best profit from prophylaxis and those where prophylaxis is not worthwhile since the baseline risk is too low. Secondly, for high-risk patients a low emetogenic anaesthesia technique should be chosen, and thirdly, these patients should additionally receive a prophylactic antiemetic cocktail. At present, butyrophenones (e.g. droperidol), 5-HT(3) receptor antagonists ("setrons") and steroids (e.g. dexamethasone) are the most rational choices for the antiemetic cocktail. Although there is strong evidence that there is an additive effect when these antiemetics are combined, economic constraints may influence the number of antiemetics that are eventually chosen. Identification of high-risk patients remains the most difficult part of the rule of three. Risk scores have been proposed and have been widely implemented in clinical practice. The sensitivity and specificity of such scores, however, remain particularly unsatisfactory. Unless more reliable risk scores are developed, aggressive treatment of established PONV symptoms may be more useful and more cost-effective than prophylaxis for many patients.     

术后恶心呕吐相关基因多态性的研究现状

背景 术后恶心呕吐(postoperative nausea and vomiting,PONV)是临床上常见的并发症,受多种因素的影响.尽管有多种类型的止吐药物用于控制PONV的发生,但效果并不理想,且患者对药物的反应存在很大的差异性. 目的 探讨基因多态性对PONV发生的影响,为预防PONV提供预警作用. 内容 多种基因多态性与PONV的发生具有关联性,其中涉及对止吐药物疗效的影响. 趋向 目前已发现多个PONV的易感基因,期待根据基因分型进行个体化治疗以优化PONV的药物防治效果.     

Gastric disorders: modifications of gastric content,antacids and drugs influencing gastric secretions and motility

Gastric disorders have clinical implications in both anaesthesia and critical care medicine. Aspiration of acidic gastric contents in the perioperative setting is linked to pneumonitis and later development of pneumonia. Pharmacological strategies to minimize this risk include histamine-2 receptor antagonists, sucralfate, proton pump inhibitors and sodium citrate. Use of gastric acid-suppressing therapy is widespread in critical care. The aim is to reduce the incidence of stress-related mucosal bleeding. Intestinal failure is common in critical illness. Medications that decrease gastric motility and contribute to ileus, include opioid analgesics, catecholamines and α₂-adrenoceptor antagonists. Current pharmacological strategies for increasing gastric motility include the use of metoclopramide and erythromycin either alone or in combination. Limited efficacy has been demonstrated with these medications. A range of further medications, with different drug targets, are being investigated as alternatives. These include motilin agonists, peripherally acting opioid receptor antagonists, cholecystokinin antagonists, 5-HT₄ antagonists and cholinesterase inhibitors.     

5-HT3 receptor antagonistsvs traditional agents for the prophylaxis of postoperative nausea and vomiting

PURPOSE: Numerous antiemetics have been studied for the prevention of postoperative nausea and vomiting (PONV) including traditional agents (metoclopramide, perphenazine, prochlorperazine, cyclizine and droperidol) and the 5-HT3 receptor antagonists (ondansetron, dolasetron, granisetron and tropisetron). The results have been divergent and inconsistent. The purpose of this quantitative systematic review was to evaluate the effectiveness of 5HT3 receptor antagonists compared to traditional antiemetics for the prevention of PONV METHODS: A systematic search of the English language literature using computerized MEDLINE, EMBASE, and Pre-MEDLINE databases from 1966 to October 1999 and a manual search of references from retrieved articles were performed. Individual efficacy and adverse effect data was extracted from each of the studies according to a predefined protocol. The summary odds ratios were calculated using the Dersimonian and Laird method under a random effects model. RESULTS: A total of 41 trials met our pre-defined inclusion criteria and were included in our analysis. Results in the 32 studies examining PONV indicated a 46% reduction in the odds of PONV in the 5-HT3-treated group (0.54 [95% CI 0.42-0.71], P < 0.001). Evaluation of PONV by traditional antiemetic agent demonstrated a 39% reduction compared with droperidol (0.61 [95% CI 0.42-0.89], P < 0.001) and a 56% reduction compared with metoclopramide (0.44 [95% CI 0.31-0.62], P < 0.001). Results in the 34 studies examining vomiting indicated a 38% reduction in the odds of vomiting in the 5-HT3-treated group (0.62 [95% CI 0.48-0.81], P < 0.001). CONCLUSIONS: The 5-HT3 receptor antagonists are superior to traditional antiemetic agents for the prevention of PONV and vomiting. The reduction in the odds of PONV and vomiting is significant in the overall analysis and the subgroup analyses comparing 5-HT3 receptor antagonists with droperidol and metoclopramide.     

Physiology and pharmacology of nausea and vomiting

Nausea and vomiting are both very unpleasant experiences. The physiology is poorly understood; however, understanding what we do know is key to tailoring a preventative or therapeutic antiemetic regime. There are two key sites in the central nervous system implicated in the organization of the vomiting reflex: the vomiting centre and the chemoreceptor trigger zone. There are five key neurotransmitters involved in afferent feedback to these areas. These are histamine (H₁ receptors), dopamine (D₂), serotonin (5-HT₃), acetyl choline (muscarinic) and neurokinin (substance P). Postoperative nausea and vomiting will occur in around one-third of elective patients who have no prophylaxis. This can result in many detrimental effects including patient dissatisfaction, unplanned admission and prolonged recovery. It is therefore essential that clinicians understand how they can prevent and treat nausea and vomiting using either a single agent or a combination of antiemetics to target relevant receptors. Commonly used drugs include antihistamines, dopamine antagonists, serotonin antagonists and steroids. More novel agents are being developed such as aprepitant, a neurokinin receptor antagonist, palonosetron, a 5HT₃ receptor antagonist, and nabilone, a synthetic cannabinoid.     

Physiology and pharmacology of nausea and vomiting

Nausea and vomiting are both very unpleasant experiences. The physiology is poorly understood; however, understanding what we do know is key to tailoring a preventative or therapeutic antiemetic regime. There are two key sites in the central nervous system implicated in the organization of the vomiting reflex: the vomiting centre and the chemoreceptor trigger zone. There are five key neurotransmitters involved in afferent feedback to these areas. These are histamine (H₁ receptors), dopamine (D₂), serotonin (5-HT₃), acetyl choline (muscarinic) and neurokinin (substance P). Postoperative nausea and vomiting will occur in around one-third of elective patients who have no prophylaxis. This can result in many detrimental effects including patient dissatisfaction, unplanned admission and prolonged recovery. It is therefore essential that clinicians understand how they can prevent and treat nausea and vomiting using either a single agent or a combination of antiemetics to target relevant receptors. Commonly used drugs include antihistamines, dopamine antagonists, serotonin antagonists and steroids. More novel agents are being developed such as aprepitant, a neurokinin receptor antagonist, palonosetron, a 5HT₃ receptor antagonist and nabilone, a synthetic cannabinoid.     

Possibilities and limitations in the pharmacological management of postoperative nausea and vomiting

The incidence of postoperative nausea and vomiting (PONV) after a standard anaesthetic technique consisting of inhalational anaesthetics and opioids and no PONV prophylaxis is up to 30%. Being one of the most common complaints following surgery under general anaesthesia, it is not surprising that PONV is a considerable cause of dissatisfaction with recovery from anaesthesia and remains one of the most commonly used items in surveys assessing patient satisfaction with the perioperative period and in scoring systems for the quality of recovery following anaesthesia. The weakest link in the chain from research to patient benefit is the implementation of well proven strategies. Rather than simply following existing consensus guidelines, anaesthesiologists should critically assess whether the algorithms introduced produce the desired effect. Risk-adapted strategies may work, but recent implementation studies suggest that compliance with these algorithms may be poor and that high-risk patients often do not receive appropriate antiemetic prophylaxis. Multimodal prevention may represent a more simple approach and, thus, a more reliable strategy to reduce the incidence of PONV. Such an approach would circumvent the inherent weaknesses of the need to undertake a risk assessment for each individual patient. Anaesthesiologists need to know about the new agents available to manage PONV, such as the NK1-antagonists or the newer 5-HT3 antagonists, but should not forget the traditional and well established antiemetics that are valuable components in the current portfolio. The low cost of most of the currently available antiemetics and the low incidence of side-effects suggests that a liberal antiemetic prophylaxis regimen is a meaningful option in order to eliminate or substantially reduce the 'big little problem'.     

Prophylaxis of postoperative nausea and vomiting: controversies in the use of serotonin 5-hydroxytryptamine subtype 3 receptor antagonists

Postoperative nausea and vomiting (PONV) continues to be a "big little problem" despite recent advances in anesthesia. Because of an increased interest in, and the abundant publications on this topic, guidelines for the management of PONV were published in 2003. Several key but controversial issues regarding PONV prophylaxis were left unaddressed, however. These included whether clinical differences exist between the 5-hydroxytryptamine subtype 3 (5-HT3) receptor antagonists, concern over optimal dosage and timing of administration, optimal 5-HT3 receptor antagonist combination therapy, and whether rescue therapy is effective after prior administration of the same or a different 5-HT3 receptor antagonist. The application of these antiemetics in clinical practice has raised questions regarding the role of the 5-HT3 receptor antagonists in the treatment of postdischarge nausea and vomiting and opioid-induced nausea and vomiting. A brief overview of the incidence, risk factors and current management recommendations for PONV and current controversies with special emphasis on the 5-HT3 receptor antagonists, is discussed.     

Prevention and treatment of postoperative nausea and vomiting in children. An evidence-based approach

Significant improvement towards an efficacious control of postoperative nausea and vomiting (PONV) has taken place recently. These improvements may be summarised using the "rule of three". That rule describes a pragmatic and rational approach of PONV control. First, identify the patient at risk using predictive factors. Second, modify the anaesthesia technique to keep the baseline risk as low as possible. Third, administer antiemetics rationally, considering their degree of efficacy, their risk, and their potential additive effects. Despite considerable research efforts, identifying the patient at high risk of PONV remains a difficult task. However, today, we understand the degree of efficacy, dose-responsiveness, and adverse effects of most antiemetics. None of those molecules should be regarded as being universally efficacious, there is no gold standard, and, when used alone, their degree of efficacy is limited. Thus, they should be combined for improved efficacy. Among the most promising molecules are butyrophenones (droperidol, haloperidol), 5-HT(3) receptor antagonists (ondansetron, dolasetron, tropisetron, granisetron), and steroids (for instance, dexamethasone). The lack of relevant paediatric PONV data remains a major drawback and is highly unsatisfactory. Hopefully, future research will further improve the control of PONV not only in adults but also in children.     

Preclinical evidence for the anxiolytic activity of 5-HT3 receptor antagonists: A review

From ancient history to present times, mankind has sought for anxiolytics, and various medications have been found and consequently used, at present culminating in heavy benzodiazepine use. Side-effects such as dependence and tolerance have always induced the need, and accordingly the search, for new and better treatments. The 5-HT_1A receptor agonists like buspirone are an example of such new therapeutic agents. Whether or not those compounds will indeed be better as well remains to be seen. Recently another new class of putative anxiolytics has been proposed, the 5-HT₃ receptor antagonists. The present article reviews the evidence for anxiolytic activity of this new class of compounds of animal models of anxiety. Compared to the established anxiolytics (benzodiazepines and, to a lesser extent, 5-HT_1A receptor agonists) 5-HT₃ receptor antagonists have a different anxiolytic profile. They are active in a limited number of animal models, they often are very potent and the ratio between therapeutic activity and side-effects is remarkably large. No evidence for tolerance or rebound effects was found, which makes them an attractive alternative to the benzodiazepines. Preliminary human clinical data are controversial; some investigators have reported positive effects in anxiety, others have not been able to demonstrate this.     

Management of postoperative nausea and vomiting in patients undergoing laparoscopic cholecystectomy

The common and distressing complications of postoperative nausea and vomiting (PONV) are the main concern of 40–70% of patients undergoing laparoscopic cholecystectomy (LC). The first step in preventing PONV after LC is to reduce the risk factors involving patient characteristics, surgical procedure, anesthetic technique, and postoperative care. Particularly, the use of propofol-based anesthesia can reduce the incidence of PONV after LC. Second, prophylactic antiemetics including antihistamines (dimenhydrinate), phenothiazines (perphenazine), butyrophenones (droperidol), benzamides (metoclopramide), dexamethasone, and serotonin receptor antagonists (ondansetron, granisetron, tropisetron, dolasetron, and ramosetron) are available for preventing PONV after LC. Third, antiemetic therapy combined with a serotonin receptor antagonist (ondansetron, granisetron) and droperidol or dexamethasone is highly effective in the prevention of PONV after LC. Fourth, acupressure at the P6 point is a nonpharmacologic technique that is as effective as ondansetron for preventing PONV after LC. Knowledge regarding the risk factors for PONV and antiemetics is needed for the management of PONV after LC.     

Dexamethasone for the prevention of postoperative nausea and vomiting: a quantitative systematic review

The role of dexamethasone in the prevention of postoperative nausea and vomiting (PONV) is unclear. We reviewed efficacy and safety data of dexamethasone for prevention of PONV. A systematic search (MEDLINE, EMBASE, Cochrane Library, hand searching, bibliographies, all languages, up to April 1999) was done for full reports of randomized comparisons of dexamethasone with other antiemetics or placebo in surgical patients. Relevant end points were prevention of early PONV (0 to 6 h postoperatively), late PONV (0 to 24 h), and adverse effects. Data from 1,946 patients from 17 trials were analyzed: 598 received dexamethasone; 582 received ondansetron, granisetron, droperidol, metoclopramide, or perphenazine; 423 received a placebo; and 343 received a combination of dexamethasone with ondansetron or granisetron. With placebo, the incidence of early and late PONV was 35% and 50%, respectively. Sixteen different regimens of dexamethasone were tested, most frequently, 8 or 10 mg IV in adults, and 1 or 1.5 mg/kg IV in children. With these doses, the number needed to treat to prevent early and late vomiting compared with placebo in adults and children was 7.1 (95% CI 4.5 to 18), and 3.8 (2.9 to 5), respectively. In adults, the number needed to treat to prevent late nausea was 4.3 (2.3 to 26). The combination of dexamethasone with ondansetron or granisetron further decreased the risk of PONV; the number needed to treat to prevent late nausea and vomiting with the combined regimen compared with the 5-HT3 receptor antagonists alone was 7.7 (4.8 to 19) and 7.8 (4.1 to 66), respectively. There was a lack of data from comparisons with other antiemetics for sensible conclusions. There were no reports on dexamethasone-related adverse effects. IMPLICATIONS: When there is a high risk of postoperative nausea and vomiting, a single prophylactic dose of dexamethasone is antiemetic compared with placebo, without evidence of any clinically relevant toxicity in otherwise healthy patients. Late efficacy seems to be most pronounced. It is very likely that the best prophylaxis of postoperative nausea and vomiting currently available is achieved by combining dexamethasone with a 5-HT3 receptor antagonist. Optimal doses of this combination need to be identified.     

Droperidol and 5-HT3-receptor antagonists, alone or in combination, for prophylaxis of postoperative nausea and vomiting. A meta-analysis of randomised controlled trials

BACKGROUND: Droperidol and 5-HT3-receptor antagonists are among the most potent antiemetics to prevent postoperative nausea and vomiting (PONV). Combinations of these drugs have been used to increase the efficacy of antiemetic treatment. However, so far the quantitative effect of this combination has not been evaluated systematically. METHODS: Results from randomised controlled trials investigating the efficacy of 5-HT3-receptor antagonists or droperidol alone versus the combination of both drugs to prevent PONV were included in a meta-analysis. Studies were systematically searched using Medline, EMBASE, the Cochrane-Library, and by manually screening the reference lists of matching review articles and current issues of locally available peer-reviewed anaesthesia journals. Seven papers with data on granisetron published by Fujii and co-workers were not considered. The main end point in each study was defined as occurrence of nausea, retching, or vomiting within 6 h ("early PONV") and within 48 h ("late PONV") after surgery. The relative risks (RR) and the numbers needed to treat (NNT) of the pooled data with their corresponding 95% confidence intervals (given in parentheses) were calculated using a random effects model. RESULTS: Eight studies with 881 patients (adults: n=801; children (mean age: 8 yr): n=80) were included in the analysis. Droperidol was applied to 340 patients, 5-HT3-receptor antagonists to 198, and 343 were treated with a combination of both drugs. Seven out of these eight studies reported increased antiemetic efficacy of the combination group compared with the single drugs (droperidol and 5-HT3-receptor antagonists respectively). However, in none of the trials did this difference reach statistical significance. When a meta-analytic analysis based on these results was performed the combination of droperidol with a 5-HT3-receptor antagonist was not associated with a significantly increased antiemetic efficacy. In 12 to 13 patients a 5-HT3-receptor antagonist has to be added to droperidol prophylaxis to prevent one additional patient from PONV who would have had suffered from PONV when treated with droperidol alone (RR "early PONV": 1.52 (0.95-2.44); RR "late PONV": 1.24 (0.89-1.74)). Similar results were obtained when the antiemetic effect of adding droperidol to a prophylaxis with 5-HT3-receptor antagonists was analysed. In this case 10 to 12 patients have to be treated with the 5-HT3-droperidol combination instead of with a 5-HT3-receptor antagonist alone to prevent one additional patient from PONV (RR "early PONV": 1.55 (0.68-3.52); RR "late PONV": 1.29 (0.77-2.17)). There were no reports of an increased incidence of adverse effects. CONCLUSION: The data on the combination of droperidol with 5-HT3-receptor antagonists suggest that there is a trend towards increased efficacy of the combination therapy compared to the single drugs. However, so far there are insufficient data to recommend this combination treatment for prophylaxis.